CLEAVAGE OF DOUBLE-STRAND DNA BY BLEOMYCI N DERIVATIVES OF OLIGONUCLEOTIDES FORMING A TERNARY COMPLEX

Hexadecathymidylate derivatives, containing covalently-bound antitumor antibiotic bleomycin Ag, were shown to form a triple-helix complex wi th double-strand 30-bp DNA-target and to carry out within this complex complementary-addressed DNA modification. Fivefold excess of reagent in relation to target leads to non-specific cleavage mainly of pyrimid ine-rich DNA strand. Total degrees of the target-strand cleavage by 5' - and 3'-bleomycin derivatives of hexadecathymidylate were 25 and 35% for purine-rich strand and 47 and 36% for pyrimidine-rich strand. Degr ees of non-specific cleavage by 5'-bleomycin derivative of hexadecanuc leotide that does not form triple-helix were 6 and 16% for purine- and pyrimidine-rich strands, respectively. Comparison of these data has s hown that site-specific cleavage prevailed nonspecific one. Tripler of 5'-bleomycin derivative with DNA melted by 5 degrees C lower (m.p. 40 degrees C) than the similar tripler of hexadecathymidylate. Temperatu re lowering from 50 to 20 degrees C increases the DNA-cleavage degree according to the increase in the part of target molecules involved in triple-helix formation.